Effectiveness of Evusheld in Immunocompromised Patients: Propensity Score-Matched Analysis.

BACKGROUND: Tixagevimab and cilgavimab, a combined monoclonal antibody (Evusheld), was granted emergency use authorization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) preexposure prophylaxis in individuals with immunocompromising conditions. In this study we used population-based real-world data to evaluate the effectiveness of Evusheld in immunocompromised patients. METHODS: Using the computerized database of the largest healthcare provider in Israel, we identified all adult immunocompromised patients who were eligible to receive Evusheld (150 mg tixagevimab and 150 mg cilgavimab) on 15 February 2022. Patients with a documentation of a prior SARS-CoV-2 infection were excluded. A total of 703 patients who received Evusheld were propensity score matched, using a ratio of 1:4, with 2812 patients who had not received Evusheld (control group). Patients were followed through 30 June 2022 for up to 90 days for the first documentation of SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19)-related hospitalization. RESULTS: Overall, 72 patients in the Evusheld group and 377 patients in the control group had SARS-CoV-2 infection, reflecting an incidence rate of 4.18 and 5.64 per 100 person-months, respectively. The hazard ratios were 0.75 (95% confidence interval [CI]: .58-.96) for SARS-CoV-2 infection and 0.41 (95% CI: .19-.89) for COVID-19-related hospitalization in the Evusheld group compared to the control group. The magnitude of relative risk reduction of each outcome was greater in nonobese patients (P for interaction = .020 and .045, respectively). CONCLUSIONS: This study suggests that Evusheld is effective in reducing the risk of SARS-CoV-2 infection and COVID-19 hospitalization in immunocompromised patients. The effectiveness of this dose appears to be greater in nonobese patients.

Effectiveness of Molnupiravir in High-Risk Patients: A Propensity Score Matched Analysis.

BACKGROUND: Molnupiravir was granted emergency use authorization for the treatment of mild to moderate coronavirus disease 2019 (COVID-19). In this study, we used population-based real-world data to evaluate the effectiveness of molnupiravir. METHODS: The database of the largest healthcare provider in Israel was used to identify all adults with first-ever positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) performed in the community during January-February 2022, who were at high risk for severe COVID-19, and had no contraindications for molnupiravir use. Patients were included regardless of SARS-CoV-2 vaccination status. A total of 2661 patients who received molnupiravir were propensity score matched with 2661 patients who have not received molnupiravir (control group). Patients were followed through 10 March 2022 for up to 28 days for the first occurrence of the composite severe COVID-19 or COVID-19-specific mortality. RESULTS: The composite outcome occurred in 50 patients in the molnupiravir group and 60 patients in the control group. Molnupiravir was associated with a nonsignificant reduced risk of the composite outcome: hazard ratio, 0.83 (95% confidence interval, .57-1.21). However, subgroup analyses showed that molnupiravir was associated with a significant decrease in the risk of the composite outcome in older patients 0.54 (0.34-0.86), in females 0.41 (0.22-0.77), and in patients with inadequate COVID-19 vaccination 0.45 (0.25-0.82). The results were similar when each component of the composite outcome was examined separately. CONCLUSIONS: This study suggests that in the era of Omicron and in real-life setting, molnupiravir might be effective in reducing the risk of severe COVID-19 and COVID-19-related mortality, particularly in specific subgroups.

Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients.

BACKGROUND: Paxlovid was granted an Emergency Use Authorization for the treatment of mild to moderate coronavirus disease 2019 (COVID-19), based on the interim analysis of the Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial. Paxlovid effectiveness needs to be assessed in a noncontrolled setting. In this study we used population-based real-world data to evaluate the effectiveness of Paxlovid. METHODS: The database of the largest healthcare provider in Israel was used to identify all adults aged 18 years or older with first-ever positive test for severe acute respiratory syndrome coronavirus 2 between January and February 2022, who were at high risk for severe COVID-19 and had no contraindications for Paxlovid use. Patients were included irrespective of their COVID-19 vaccination status. Cox hazard regression was used to estimate the 28-day hazard ratio (HR) for severe COVID-19 or mortality with Paxlovid examined as time-dependent variable. RESULTS: Overall, 180 351 eligible patients were included; of these, only 4737 (2.6%) were treated with Paxlovid, and 135 482 (75.1%) had adequate COVID-19 vaccination status. Both Paxlovid and adequate COVID-19 vaccination status were associated with significant decrease in the rate of severe COVID-19 or mortality with adjusted HRs of 0.54 (95% confidence interval [CI], .39-.75) and 0.20 (95% CI, .17-.22), respectively. Paxlovid appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease (interaction P < .05 for all). No significant interaction was detected between Paxlovid treatment and COVID-19 vaccination status. CONCLUSIONS: This study suggests that in the era of Omicron and in real-life settings, Paxlovid is highly effective in reducing the risk of severe COVID-19 or mortality.

Exploring resilience in public services within marginalised communities during COVID-19: The case of coal mining regions in Colombia.

This paper examines the impact of COVID-19 on marginalised communities and its effects on the provision of public services. Focusing on two coal mining regions in Colombia during the pandemic crisis, and examining Indigenous and Afro-Colombian communities, we analyze the provision of public services at a local level, identifying both shortcomings and resilience. Findings show that the lack of resilient public services amplified the effects of COVID-19 and its containment measures, exacerbating existing structural inequalities within local marginalised communities. It also reinforced the control exercised by coal mining companies within local economies. However, the substantial lack of public service provision also provided space for the development and strengthening of several resilience strategies among local communities, such as solidarity networks and schemes and the revitalization of local environmental knowledge. The study identifies multiple shortcomings in how the national and local administrations handled the COVID-19 outbreak and highlights the potential of enhancing resilience in public services to support marginalised communities in times of crisis.

Characteristics of endovascular pneumococcal infections; a decade of nationwide surveillance study.

In order to characterize pneumococcal endovascular infection in the post-vaccination era, a retrospective nationwide study based on the Israeli Adult IPD database was conducted. Between 2010 and 2019, 0.6% (23 cases) of IPD cases were of endovascular type, occurring mainly in males (72.3%) with underlying medical conditions (78.2%). Additional pneumococcal source (10 patients) and concomitant infections were not uncommon. Penicillin and ceftriaxone susceptibility rates were 65.2% and 91.3%, respectively; 60.9% of the isolates were not covered by the pneumococcal conjugate vaccine. 21.7% of patients died during hospitalization. In conclusion, pneumococcal endovascular infections still carry significant morbidity and mortality.

Non-inferiority of metronidazole to vancomycin in the treatment of first episode non-severe Clostridioides difficile infection: a single center retrospective cohort study.

OBJECTIVES: We sought to assess the effectiveness of oral vancomycin compared to metronidazole on recurrence and mortality among hospitalized patients with non-severe Clostridioides difficile infection (CDI). METHODS: A single center retrospective cohort study was conducted, including adult patients hospitalized between 2015 and 2020 with a first episode of non-severe CDI, treated with metronidazole or vancomycin as monotherapy for at least 10 days. We assessed recurrence of CDI requiring hospitalization (primary outcome) and all-cause mortality up to 8 weeks, post discharge. RESULTS: Overall, 160 patients were treated with vancomycin and 149 treated with metronidazole. Re-hospitalization within 8 weeks due to CDI occurred in 10 (6.2%) patients in the vancomycin group, and 13 (8.7%) in the metronidazole group (P value = 0.407). Eight-week mortality occurred in 39 patients (26.2%) in the metronidazole group and 46 patients (28.8%) in the vancomycin group (P value = 0.61). After adjusting for age, gender, Ischemic heart disease, white blood cell count, neutrophile count and CRP, there was no significant difference between the two treatments (Re-hospitalization in 8 weeks due to CDI P = 0.5059; In-hospital death P = 0.7950; 4-week mortality P = 0.2988; 8-week mortality P = 0.8237). CONCLUSION: There is no benefit of using vancomycin compared to metronidazole concerning recurrence rate requiring hospitalization, in-hospital and up to 4- and 8-week mortality rate in non-severe first episode of CDI.

Spotted Fever Group Rickettsioses in Israel, 2010-2019.

In a multicenter, nationwide, retrospective study of patients hospitalized with spotted fever group rickettsiosis in Israel during 2010-2019, we identified 42 cases, of which 36 were autochthonous. The most prevalent species was the Rickettsia conorii Israeli tick typhus strain (n = 33, 79%); infection with this species necessitated intensive care for 52% of patients and was associated with a 30% fatality rate. A history of tick bite was rare, found for only 5% of patients; eschar was found in 12%; and leukocytosis was more common than leukopenia. Most (72%) patients resided along the Mediterranean shoreline. For 3 patients, a new Rickettsia variant was identified and had been acquired in eastern, mountainous parts of Israel. One patient had prolonged fever before admission and clinical signs resembling tickborne lymphadenopathy. Our findings suggest that a broad range of Rickettsia species cause spotted fever group rickettsiosis in Israel.

[VERTEBRAL OSTEOMYELITIS CAUSED BY RARE PATHOGENS--THE NEED FOR HIGH INDEX OF SUSPICION].

Vertebral OsteomyeLitis (V.O.) is a rare event that usually presents insidiously and follows an indolent clinical course, making early diagnosis difficult. The most important infecting organism in V.O. is Staphylococcus aureus, followed by gram-negative bacilli. We describe herein two cases of V.O. hospitalized in our department during the same week, caused by rare pathogens--Streptococcus sanguis (viridans) and Bacteroides fragilis. V.O. must be recognized rapidly because delay in diagnosis and treatment can result in neurologic compromise and high mortality. Its prompt and accurate diagnosis depends on detailed knowledge of the disease along with a high index of suspicion, even in face of rare pathogens on bacteriology results.

Asymptomatic carriage of Pneumocystis jirovecii and cytomegalovirus in lungs of immunocompetent patients.

PURPOSE: Pneumocystis jirovecii (PCP) and cytomegalovirus (CMV) are opportunistic pathogens which cause lung infection in immunocompromised individuals. However, scarce data are available regarding the carriage of CMV or PCP in immunocompetent, non critically ill patients. The purpose of this study was to evaluate the prevalence of PCP and CMV in broncholaveolar lavage of adult immunocompetent, non critically ill patients. METHODS: BAL fluids from immunocompetent patients who underwent bronchoscopy were analyzed by polymerase chain reaction (PCR) for CMV and PCP DNA. We tested CMV antibodies in serum. In patients with positive CMV DNA in lavage fluid, we further analyzed peripheral blood for the presence of CMV DNA. RESULTS: Ninety three patients were included. We did not detect PCP DNA in BAL in any patient. CMV DNA was found in BAL of 5 of 86 CMV IgG positive patients (5.8 %). Patients who were positive for CMV did not differ from patients with negative PCR for CMV regarding demographic and clinical features. CONCLUSION: We did not find PCP colonization in our cohort of patients. However, we found significant prevalence of CMV DNA in BAL from immunocompetent patients, with no evidence of acute CMV infection. This finding may represent colonization by CMV in immunocompetent, non-critically ill individuals.

Secondary prophylaxis for Clostridioides difficile infection for patients on non-C. difficile antibiotics: a retrospective cohort study.

OBJECTIVES: Recurrent Clostridioides difficile infection (CDI) poses healthcare challenges and morbidity. Preventing recurrence with prophylactic oral CDI antibiotics lack consensus. METHODS: We used data from the largest healthcare provider in Israel to identify all adults aged 18 years or older diagnosed with a first episode of CDI (Index CDI) between February 2018 and December 2022 and subsequently received a non-CDI antibiotic within 2-8 weeks. Patients who received a concurrent prophylactic CDI antibiotic constituted the CDI prophylaxis group. Multivariable Cox proportional hazard regression models were used to examine the association of secondary CDI prophylaxis with CDI recurrence according to the severity of the index CDI (primary objective) and with 4- and 8-week all-cause mortality (secondary objective). RESULTS: A total of 434 eligible patients were included. Among them, 327 did not receive CDI antibiotic prophylaxis, while 107 did. CDI antibiotic prophylaxis was associated with a significant risk reduction of CDI recurrence with an adjusted HR of 0.51 (95% CI, 0.27-0.97). The magnitude of the association was modified by the severity of the index CDI episode (P for interaction 0.0182). Specifically, the HR for recurrence was 0.163 (95% CI 0.045-0.593) for non-severe CDI, and 1.242 (95% CI 0.524-2.946) for severe CDI. No significant association was found between CDI antibiotic prophylaxis and 4-8 weeks mortality. CONCLUSION: Secondary prophylaxis with CDI antibiotics appears to be associated with a reduced risk of recurrence in patients with previous non-severe CDI episode. Further studies are needed to confirm this finding.

Laparoscopic approach for the treatment of acute complications after appendectomy: a systematic review.

INTRODUCTION: The significance of laparoscopy after appendectomy is still unclear, despite the fact that it is thought to be an appropriate technique for the detection and management of postoperative complications. We aimed to determine the incidence, risk factors, diagnosis, and laparoscopic approach for the treatment of acute complications after appendectomy performing a systematic review of the literature. EVIDENCE ACQUISITION: We performed systematic review of the PubMed/MEDLINE, Embase and GoogleScholar bibliographic databases between 1995 and 2022 regarding laparoscopic resolution of early postoperative complications after appendectomy. Demographics, peri-operative variables, and postoperative outcomes were analyzed. EVIDENCE SYNTHESIS: A total of 9 studies comprising 116 cases of laparoscopic resolution of early complications after appendectomy were included. The primary surgery showed a 60% of perforated or gangrenous appendicitis. Time elapse between the appendectomy and the diagnosis of the postoperative complication was from 2 to 15 days (median 5.8 days). The procedures performed at laparoscopy were as follows: laparoscopic washout and drainage of generalized peritonitis and intra-abdominal abscesses (95.6%), laparoscopic lysis of adhesions due to small bowel obstruction (1.7%), running suturing for unnoticed small bowel lesion (1.7%) and one patient required a right colectomy due to stump leakage (0.8%). Conversion to an open approach was necessary in 9 patients (7.8%). Postoperative complications after early re-laparoscopy washout were reported in 4 publications (15.5%). Finally, 15 (12.9%) patients required an additional intervention. The mean LOS was of 5 days. CONCLUSIONS: Infectious complications are not uncommon after appendectomy, but their incidence increases significantly in complicated appendicitis, with IAA being the most feared complication. When re-exploration is mandatory, the laparoscopic approach is a safe and highly effective tool for the diagnosis and treatment of these complications, adding the benefits of minimally invasive surgery.

Association Between COVID-19 Infection and Pulmonary Fibrosis: A Nested Case-Control Study.

BACKGROUND: Pulmonary fibrosis is associated with significant morbidity. Data are scarce on the link between coronavirus disease (COVID-19) and pulmonary fibrosis. We aimed to assess the association between COVID-19 with pulmonary fibrosis. METHODS: We conducted a nested case-control study in a cohort of 2,894,801 adults without a diagnosis of pulmonary fibrosis. The underlying cohort consisted of members of the largest healthcare provider in Israel aged 18 years or older as of May 1, 2020. Subjects were followed up from cohort entry until June 30, 2022, for the occurrence of pulmonary fibrosis. Ten randomly selected controls were matched to each case of pulmonary fibrosis on age, sex, and calendar time. To account for surveillance bias a lag time of 60 days was used for ascertainment of prior COVID-19 and COVID-19 severity. RESULTS: During follow-up 1284 patients were newly diagnosed with pulmonary fibrosis and matched with 12,840 controls. Multivariable conditional logistic-regression models showed that the odds ratio for pulmonary fibrosis was 1.80 (95% confidence interval, 1.47-2.19) in patients with COVID-19 compared with no COVID-19. The multivariable odds ratio for pulmonary fibrosis was 1.33 (1.06-1.68), 2.98 (1.16-7.65), and 9.30 (5.77-14.98) for mild, moderate, and severe COVID-19, respectively, compared with no COVID-19. The magnitude of the association was attenuated but remained statistically significant for severe disease when the lag time was extended to 180 days (1.08 [0.78-1.49], 2.37 [0.75-7.46], and 5.34 [2.75-10.36] for mild, moderate, and severe COVID-19, respectively). CONCLUSIONS: COVID-19 appears to be associated with an increased risk of pulmonary fibrosis and the magnitude of the association increases with COVID-19 severity.

Unveiling the hidden threat of carbapenemase-producing Enterobacteriaceae in hospital water environments: A single-center study.

This retrospective study examined the presence of carbapenemase-producing Enterobacteriaceae in hospital water environments. Results showed that carbapenemase-producing Enterobacteriaceae was detected in 41.5% of the samples within 1 m of a water source (showers or sinks), with 20.6% of the positive samples associated with shower water sources.

Correlates of protection for booster doses of the SARS-CoV-2 vaccine BNT162b2.

Vaccination, especially with multiple doses, provides substantial population-level protection against COVID-19, but emerging variants of concern (VOC) and waning immunity represent significant risks at the individual level. Here we identify correlates of protection (COP) in a multicenter prospective study following 607 healthy individuals who received three doses of the Pfizer-BNT162b2 vaccine approximately six months prior to enrollment. We compared 242 individuals who received a fourth dose to 365 who did not. Within 90 days of enrollment, 239 individuals contracted COVID-19, 45% of the 3-dose group and 30% of the four-dose group. The fourth dose elicited a significant rise in antibody binding and neutralizing titers against multiple VOCs reducing the risk of symptomatic infection by 37% [95%CI, 15%-54%]. However, a group of individuals, characterized by low baseline titers of binding antibodies, remained susceptible to infection despite significantly increased neutralizing antibody titers upon boosting. A combination of reduced IgG levels to RBD mutants and reduced VOC-recognizing IgA antibodies represented the strongest COP in both the 3-dose group (HR = 6.34, p = 0.008) and four-dose group (HR = 8.14, p = 0.018). We validated our findings in an independent second cohort. In summary combination IgA and IgG baseline binding antibody levels may identify individuals most at risk from future infections.

Antibiotic exposure as a risk factor for fluconazole-resistant Candida bloodstream infection.

Recent exposure to azoles is an important risk factor for infection with fluconazole-resistant Candida spp., but little is known about the role of antibacterial drug exposure in the emergence of drug-resistant Candida. We did a prospective nationwide surveillance study of candidemia in Israel and analyzed the propensity score-adjusted association between antifungal and antibacterial drug exposure and bloodstream infection with C. glabrata and fluconazole-resistant Candida isolates. Four hundred forty-four episodes of candidemia (450 Candida isolates, 69 [15%] C. glabrata isolates, and 38 [8.5%] fluconazole-resistant isolates) from 18 medical centers in Israel were included. C. glabrata bloodstream infection was strongly associated with recent metronidazole exposure (odds ratio [OR], 3.2; P < 0.001). Infection with a fluconazole-resistant isolate was associated with exposure to carbapenems, trimethoprim-sulfamethoxazole, clindamycin, and colistin (odds ratio, 2.8; P = 0.01). The inclusion of antibacterial drug exposure in a multivariable model significantly enhanced the model's predictive accuracy for fluconazole-resistant Candida bloodstream infection. Our findings may be relevant to the selection of empirical antifungal treatment and broaden the scope of antibiotic-associated collateral damage.

Assessment of disease-severity scoring systems for patients with sepsis in general internal medicine departments.

INTRODUCTION: Due to the increasing burden on hospital systems, most elderly patients with non-surgical sepsis are admitted to general internal medicine departments. Disease-severity scoring systems are used for stratification of patients for utilization management, performance assessment, and clinical research. Some widely used scoring systems for septic patients are inappropriate when rating non-surgical patients in a non-intensive care unit (ICU) environment mainly because their calculations require types of data that are frequently unavailable. This study aimed to assess the fitness of four scoring systems for septic patients hospitalized in general internal medicine departments: modified early warning score (MEWS), simple clinical score (SCS), mortality in emergency department sepsis (MEDS) score, and rapid emergency medicine score (REMS). METHODS: We prospectively collected computerized data of septic patients admitted to general internal medicine departments in our community-based university hospital. We followed 28-day in-hospital mortality, overall in-hospital mortality, and 30- and 60-day mortality. Using a logistic regression procedure we calculated the area under ROC curve (AUC) for every scoring system. RESULTS: Between February 1st, 2008 and April 30th, 2009 we gathered data of 1,072 patients meeting sepsis criteria on admission to general internal medicine departments. The 28-day mortality was 19.4%. The AUC for the MEWS was 0.65-0.70, for the SCS 0.76-0.79, for the MEDS 0.73-0.75, and for the REMS, 0.74-0.79. Using Hosmer-Lemeshow statistics, a lack of fit was found for the MEDS model. All scoring systems performed better than calculations based on sepsis severity. CONCLUSIONS: The SCS and REMS are the most appropriate clinical scores to predict the mortality of patients with sepsis in general internal medicine departments.

Exploring factors associated with acquisition and chronicity of infection in bronchiectasis: A population-based study.

INTRODUCTION: Chronic infection is associated with adverse outcomes among people with bronchiectasis. However, it is not known which factors are associated with a bacterial infection, and with persistence of an infection after the first episode. We aimed to determine factors associated with a new infection and with chronicity of Pseudomonas aeruginosa (PA) and H. influenzae (HI), the most common organisms in bronchiectasis infection. METHODS: Using an Israeli population database, we identified individuals diagnosed with bronchiectasis. Cox proportional hazard models were used to assess risk factors for first isolation and Logistic regression for chronicity of infection after a first isolation of PA and HI. RESULTS: We included 1305 people with a median of 5 respiratory samples per individual. PA was initially isolated in 297 people, of whom 97 (33%) developed chronic PA infection. HI was newly identified in 169 people, of whom 39 (23%) developed chronic infection (p = 0.029). Factors associated with increased risk of a new infection with PA were COPD (HR 1.87 [1.52-2.28], previous isolation of HI (HR 1.38 [1.07-1.78]), and alcohol abuse (HR 2.22 [1.13-4.3]). Younger age was associated with increased risk of HI infection, while COPD was associated with a lower risk of HI infection. Prescription of an anti- PA antibiotic was associated with chronic PA after a new infection (OR = 1.8 [1.09-2.9], p = 0.02). A landmark analysis showed that survival was worse in people with chronic PA infection vs. single or intermittent infection (Log rank: p = 0.034) CONCLUSIONS: Younger age and presence of PCD are associated with a new isolation of HI. A new infection with PA is associated with previous HI infection, PCD, COPD, and alcohol abuse. Unexpectedly, treatment with appropriate anti-PA antimicrobials was not associated with a reduced risk of chronicity.

Increased Capsule Thickness and Hypermotility Are Traits of Carbapenem-Resistant Acinetobacter baumannii ST3 Strains Causing Fulminant Infection.

BACKGROUND: Acinetobacter baumannii is a successful nosocomial pathogen, causing severe, life-threatening infections in hospitalized patients, including pneumonia and bloodstream infections. The spread of carbapenem-resistant Acinetobacter baumannii (CRAB) strains is a major health threat worldwide. The successful spread of CRAB is mostly due to its highly plastic genome. Although some virulence factors associated with CRAB have been uncovered, many mechanisms contributing to its success are not fully understood. METHODS: Here we describe strains of CRAB that were isolated from fulminant cases in 2 hospitals in Israel. These isolates show a rare hypermucoid (HM) phenotype and were investigated using phenotypic assays, comparative genomics, and an in vivo Galleria mellonella model. RESULTS: The 3 isolates belonged to the ST3 international clonal type and were closely related to each other, as shown by Fourier-transform infrared spectroscopy and phylogenetic analyses. These isolates possessed thickened capsules and a dense filamentous extracellular polysaccharides matrix as shown by transmission electron microscopy (TEM), and overexpressed the capsule polysaccharide synthesis pathway-related wzc gene. CONCLUSIONS: The HM isolates possessed a unique combination of virulence genes involved in iron metabolism, protein secretion, adherence, and membrane glycosylation. HM strains were more virulent than control strains in 2 G. mellonella infection models. In conclusion, our findings demonstrated several virulence factors, all present in 3 CRAB isolates with rare hypermucoid phenotypes.